Membrane functions are unquestionably mediated by membrane proteins. Furthermore, many membrane proteins are dependent upon their lipid environment, although with various degrees of specificity. Local anesthetics, known for their ability to block sodium conductance in excitable membranes, could therefore affect membrane function either by binding directly to membrane proteins or by disrupting the functionally required lipid-protein interaction. Our research goal is to test the validity of each of these two possibilities. Our recently developed computer-assisted ESR technique, with the use of spin-labeled local anesthetics, permits quantitative determination of local anesthetic binding. The method is uniquely useful in gathering data on the differential binding of local anesthetics to the major molecular components of the membrane (i.e., unchanged lipids, acidic phospholipids, and membrane proteins). The information can then be correlated to the functional changes resulting from such binding.